Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan.
J Biomed Mater Res A. 2020 May;108(5):1159-1170. doi: 10.1002/jbm.a.36890. Epub 2020 Feb 4.
An implantable scaffold-based vaccination system is a promising platform to generate robust immune responses by modulating the immune system. However, establishment of an effective vaccine using a biodegradable, cell-infiltrative scaffold remain challenging. Here we demonstrate a biodegradable, nanocellulose-based immune scaffold capable of sustainably activating immune cells to elicit cellular immunity. Cell-infiltrative nanocellulose hydrogels were used as a delivery carrier and cellular scaffold microenvironment. Nanofibrous hydrogels allowed for high cell infiltration and delivery of antigen-loaded nanocellulose while cells degraded the hydrogel matrix. Importantly, antigen-loaded nanocellulose hydrogels exhibited sustained activation of macrophages in vitro compared to free antigen and collagen scaffold. Histological observation revealed infiltration of macrophages and dendritic cells into the nanocellulose scaffold subcutaneously implanted in mice. In vivo fluorescence imaging indicated that the implanted scaffold released antigens at a zero-order release profile without burst diffusion. Antigen-loaded nanocellulose hydrogels increased interferon-γ-producing cells compared to free antigen injection, suggesting the enhancement of cellular immunity. Thus, nanocellulose immune scaffold may serve as a sustained-immunostimulatory vaccine platform by providing favorable microenvironments for immune cells thus enhancing vaccine efficacy.
一种基于可植入支架的疫苗接种系统是一种有前途的平台，通过调节免疫系统来产生强大的免疫反应。然而，利用可生物降解、细胞浸润的支架来建立有效的疫苗仍然具有挑战性。在这里，我们展示了一种可生物降解的基于纳米纤维素的免疫支架，能够持续激活免疫细胞以引发细胞免疫。细胞浸润性纳米纤维素水凝胶可用作递送载体和细胞支架微环境。纳米纤维水凝胶允许高细胞浸润和负载抗原的纳米纤维素的递送，同时细胞降解水凝胶基质。重要的是，与游离抗原和胶原支架相比，负载抗原的纳米纤维素水凝胶在体外能持续激活巨噬细胞。组织学观察显示，巨噬细胞和树突状细胞浸润到皮下植入小鼠的纳米纤维素支架中。体内荧光成像表明，植入的支架以零级释放模式释放抗原，没有爆发扩散。与游离抗原注射相比，负载抗原的纳米纤维素水凝胶增加了产生干扰素-γ的细胞，表明增强了细胞免疫。因此，纳米纤维素免疫支架可以作为一种持续免疫刺激疫苗平台，为免疫细胞提供有利的微环境，从而提高疫苗的疗效。
